The primary goal of The Ohio State University / M.D. Anderson Thyroid Cancer SPORE is to improve the outcomes and lives of patients with thyroid cancer by identifying genetically at-risk individuals allowing for early diagnosis and prediction of tumor behavior, developing new approaches to minimize side effects of treatments, and developing better biomarkers and treatment options for progressive metastatic disease. Several factors support the importance of applying these efforts to thyroid cancer: 1) Thyroid cancer incidence is rising at the fastest rate of all malignancies in the United States and worldwide; it s now the 5th most common malignancy in women and 11th most common in men. 2) Thyroid cancer typically takes an indolent course, thus with the increasing incidence there is an ever enlarging population of individuals (-500,000) surviving long term, many of whom suffer from lifelong effects of initial therapy. 3) For patients with more aggressive forms of thyroid cancer, such as medullary cancer (MTC), there exist no curative therapies or biomarkers that accurately predict outcome from disease or response to particular treatments thereby limiting efforts to individualize therapeutic intensity. In order to achieve our goals, this SPORE application proposes to support a multi-institutional team of experienced investigators from two of the leading institutions in the field with a history of collaborative clinical trials. We have chosen t focus on critical areas of need for rapid translation into clinical practice for thyroid cancer patients with the following four Projects supported by outstanding Cores: 1) Low-penetrance genes in the predisposition to papillary thyroid carcinoma; 2) Biomarker discovery and personalized intervention of radioiodine induced salivary gland damage in thyroid cancer patients; 3) Developing combination therapies for Medullary Thyroid Cancer; and 4) Development and validation of novel circulating medullary thyroid cancer markers. Through these translational Projects, as well as Career Developmental and Developmental Research Programs, we aim to impact on critical areas of need in thyroid cancer clinical management for all forms of thyroid cancer.